TY - JOUR
T1 - Recombinant cytomegalovirus glycoprotein B vaccine: Rethinking the immunological basis of protection
JF - Proceedings of the National Academy of Sciences
JO - Proc Natl Acad Sci USA
SP - 6110
LP - 6112
DO - 10.1073/pnas.1806420115
VL - 115
IS - 24
AU - Schleiss, Mark R.
Y1 - 2018/06/12
UR - http://www.pnas.org/content/115/24/6110.abstract
N2 - Development and licensure of a vaccine against human CMV infection is a major public health priority. Although the major driving force for a CMV vaccine is prevention of congenital infection—since CMV is the most common viral cause of permanent neurodevelopmental disability in infants globally (1)—other patient populations, in particular recipients of hematopoietic stem cells and solid organ transplant (SOT) patients, could benefit from a vaccine. A number of CMV vaccines have been evaluated in clinical trials in recent years (2). These have included live, attenuated vaccines; vectored vaccines expressing CMV-encoded immunogens; and purified recombinant protein vaccines coadministered with adjuvant. The most extensively studied vaccine to date is a subunit vaccine based on the viral envelope glycoprotein B (gB; gpUL55). Two important papers published in PNAS (3, 4) provide surprising and novel insights into the protecting mechanisms conferred by this gB vaccine.How did the CMV gB emerge as a leading vaccine candidate? CMV gB is a type 1 envelope glycoprotein and class III viral fusogen (5). It is synthesized as a 906- or 907-aa polypeptide (depending upon the strain of CMV) that undergoes extensive posttranslational modification, including glycosylation at N- and O-linked sites, followed by cleavage by the ubiquitous cellular endoprotease, furin, into amino (gp90)- and carboxy (gp58)-terminal moieties (refs. 6 and 7 and Fig. 1). The gp90 and gp58 subunits are covalently connected by disulfide bonds and the mature, glycosylated gB assumes a trimeric configuration; the trimer subsequently dimerizes as the protein assumes its final envelope conformation (8). CMV gB interacts with the virally encoded glycoprotein H/L (gH/gL) complex as an essential component of the core fusion machinery required for infection and cell-to-cell spread of virus (9). Up to 70% of the virus-neutralizing capacity of CMV immune sera recognizes gB (10). Although recent studies of anti-CMV … ↵1Email: schleiss{at}umn.edu.
ER -